Indeed, basal levels of these factors, meaning Aβ concentration at picomolar to nanomolar range (Kamenetz et al., 2003; Deshpande et al., 2009; Yankner and Lu, 2009), non-hyperphosphorylated and low nanomolar concentration of tau (Avila et al., 2004; Iqbal et al., 2005; Goedert and Spillantini, 2006) and low ApoE4/ApoE3 ratio (Huang and Mahley, 2014; Mahley and Huang, 2012; Kim et al., 2014) are positive regulators of myelination, while their increased expression or disrupted structure during Alzheimer's Disease progression lead to myelin destabilization and neuronal deficits (Figure 1). This evidence concerns the gene APOE and Alzheimer disease.